Principal Investigator/Program Director (Last, First, Middle): Morris, Martha Clare This R01 application, entitled ?Diet Patterns and Alzheimer's Disease and Other Dementia Neuropathologies? is a revised submission in response to PAR-15-356. By the year 2050 it is projected that there will be 13.5 million Americans with AD at a cost of $1.1 trillion. Currently there is no cure for AD and no effective treatments. Preventive therapies are thus crucial for heading off a public health crisis. It is estimated that delaying dementia onset by just 5 years will reduce the cost and prevalence of the disease by half. Lifestyle interventions are an excellent strategy for population- wide impact. There is considerable epidemiological evidence linking diet to AD prevention, supported by underlying biologic mechanisms in the disease etiology for individual nutrients. In addition, a large number of AD risk factors have a demonstrated dietary basis. Dietary patterns including the DASH and Mediterranean diets and a hybrid of these diets called MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) have been related to slower rates of cognitive decline and decreased incidence of AD. To date there has not been a study that has related dietary patterns to Alzheimer disease brain neuropathology or other neuropathologies associated with dementia. The clinical-neuropathologic cohort study, the Rush Memory and Aging Project affords the unique opportunity to investigate the relation of these healthy diet patterns to brain neuropathologies and to brain health. The extensive clinical and dietary data obtained among 600 hundred study participants with autopsy data will allow for unprecedented examination of diet pattern relations to multiple neuropathologies associated with AD dementia (amyloid plaques, neurofibrillary tangles, and CERAD, Braak, and NIA Reagan scores), vascular dementia (macro- and micro-infarcts, TDP-43, atherosclerosis, arteriosclerosis, cerebral amyloid angiopathy), other dementias (Lewy bodies, hippocampal sclerosis) and presynaptic proteins, a measure of brain health and cognitive reserve. The study will also examine the potential mediating roles of brain neuropathologies and of presynaptic proteins on the MIND, DASH, and Mediterranean dietary pattern associations with decline in cognitive function and clinical dementia. The study will advance the science by identifying the neuropathologic biomechanisms underlying dietary relationships to cognitive decline, AD and other dementias. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page